Linked Life Data

9174246

Source:http://linkedlifedata.com/resource/pubmed/id/9174246

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-7-24
pubmed:abstractText
Although chronic sublethal hypoxia has been shown to promote angiogenesis in the developing brain, the pathogenesis of this response is unknown. We hypothesized that this response may be mediated in part by vascular endothelial growth factor (VEGF). We reared newborn rats (P3) in a chamber with FIO2 of 9.5 +/- 1% (exposed, E). At P33, the animals were removed from the chamber and the brains prepared for immunohistochemistry, mRNA extraction, or horseradish peroxidase (HRP) permeability studies. We also isolated beagle brain germinal matrix endothelial cells from PND 1 beagle pups and placed them in three-dimensional (3-D) coculture with PND 1 rat forebrain astrocytes. Cultures were grown for 6 days in 11% O2 and compared to control 3-D cocultures. When compared to age-matched controls, the experimental rats had significantly increased cortical vascular density (vessels/mm2: 518 +/- 18 vs. 400 +/- 15, P = 0.025). HRP studies demonstrated significantly increased permeability in all cortical vessels examined in experimental rats compared to controls. Compared to controls, VEGF mRNA from hypoxic pups was increased 2.4 times, and immunohistochemical studies of VEGF protein confirmed this finding. Similarly, when compared to controls, hypoxic cocultures of brain microvascular endothelial cells and astrocytes demonstrated significant increase in tubelike structures representing in vitro angiogenesis. Additionally, astrocyte VEGF protein levels increased 4.4-fold in hypoxic compared to control astrocyte cultures and VEGF protein levels increased 1.7-fold in hypoxic compared to control cocultures. Finally, addition of VEGF (10 ng/ml culture medium) to BBMEC alone in 3-D culture elicited not only significant proliferation (P = 0.001) but also increased tube formation. These data demonstrate that the developing brain responds to chronic sublethal hypoxia with increases in permeability and angiogenesis and suggest that VEGF mediates this response.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0165-3806
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
52-61
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9174246-Animals, pubmed-meshheading:9174246-Animals, Newborn, pubmed-meshheading:9174246-Astrocytes, pubmed-meshheading:9174246-Cell Division, pubmed-meshheading:9174246-Cell Hypoxia, pubmed-meshheading:9174246-Cells, Cultured, pubmed-meshheading:9174246-Cerebral Cortex, pubmed-meshheading:9174246-Coculture Techniques, pubmed-meshheading:9174246-Endothelial Growth Factors, pubmed-meshheading:9174246-Endothelium, Vascular, pubmed-meshheading:9174246-Hypoxia, Brain, pubmed-meshheading:9174246-Lymphokines, pubmed-meshheading:9174246-Microcirculation, pubmed-meshheading:9174246-Neovascularization, Pathologic, pubmed-meshheading:9174246-Neovascularization, Physiologic, pubmed-meshheading:9174246-RNA, Messenger, pubmed-meshheading:9174246-Rats, pubmed-meshheading:9174246-Rats, Sprague-Dawley, pubmed-meshheading:9174246-Transcription, Genetic, pubmed-meshheading:9174246-Vascular Endothelial Growth Factor A, pubmed-meshheading:9174246-Vascular Endothelial Growth Factors
pubmed:year
1997
pubmed:articleTitle
Vascular endothelial growth factor mediates reactive angiogenesis in the postnatal developing brain.
pubmed:affiliation
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.